痛风汤作用机制的网络药理学和分子对接探讨  

AN INVESTIGATION OF MECHANISM OF ACTION OF GOUT DECOCTION USING NETWORK PHARMACOLOGY AND MOLECULAR DOCKING APPROACHES

作　　者：温新丽 贺玉伟 薛晓梅 吴欣 贾兆通[1] WEN Xinli;HE Yuwei;XUE Xiaomei;WU Xin;JIA Zhaotong(Department of Endocrinology and Metabology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China)

机构地区：[1]青岛大学附属医院内分泌与代谢性疾病科,山东青岛266003 [2]青岛大学附属医院山东省代谢性疾病重点实验室,山东青岛266003 [3]青岛大学代谢病研究院,山东青岛266003

出　　处：《青岛大学学报（医学版）》2021年第6期846-851,共6页Journal of Qingdao University(Medical Sciences)

基　　金：国家自然科学基金青年科学基金项目(81900636)。

摘　　要：目的基于网络药理学和分子对接方法,探究痛风汤治疗痛风的可能作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)、中国中药整合数据库(TCMID)、Similarity Ensemble Approach数据库(SEA),检索并收集痛风汤的活性成分及其对应的靶点。通过人类基因组注释数据库(Genecards)查找痛风发病相关基因,使用Cytoscape 3.7.1软件构建痛风汤的“药材-成分-靶点”网络、痛风汤各成分作用靶点间的蛋白-蛋白相互作用(PPI)网络和痛风靶点之间的PPI网络。利用DAVID生物信息资源数据库对痛风汤的作用靶点及痛风发病相关靶点进行KEGG通路富集分析,利用SwissTargetPrediction数据库预测痛风汤活性成分的真实靶点,通过SwissDock进行分子对接。结果共从痛风汤中筛选得到82个候选活性成分,并筛选出其成分相关靶点基因244个,痛风致病基因978个。通过KEGG分析找到痛风汤与痛风作用的共同通路,包括Pathway in cancer、NOD-like receptor signaling pathway、Toll-like receptor signaling pathway、T cell receptor signaling pathway,其中Pathway in cancer是最关键通路。通路中的最关键靶点为TP53,作用于TP53的化合物为土茯苓和红花中的槲皮素(Quercetin)、红花中的木犀草素(Luteolin)、苍术中的汉黄芩素(Wogonin)。通过靶点预测发现了槲皮素中有59个真实靶点与TP53相互作用,木犀草素中25个真实靶点与TP53相互作用,汉黄芩素中有2个真实靶点与TP53相互作用。在木犀草素、槲皮素真实靶点中分别选取FLT3、MAOA与相应化合物进行分子对接;选取NOS2、PTGS2与汉黄芩素做分子对接。结论痛风汤活性成分可调控痛风发病相关信号通路。Objective To explore the possible mechanism of action of gout decoction in the treatment of gout using network pharmacology and molecular docking approaches.Methods The active components of gout decoction and its corresponding targets were searched for in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrated Database(TCMID),and the Similarity Ensemble Approach(SEA).The human genome annotation database Genecards was used to search for genes associated with the development of gout;Cytoscape 3.7.1 was used to build the“herb-component-target”network of gout decoction,protein-protein interaction(PPI)network of various component targets of gout decoction,and the PPI network between the targets of gout.The bioinformatic resource database,Database for Annotation,Visualization,and Integrated Discovery,was used to perform Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis for targets of gout decoction and targets associated with the development of gout;SwissTargetPrediction was used to predict the actual targets of active components in gout decoction;SwissDock was used to perform molecular docking.Results Totally 82 candidates for active components were screened out from the gout decoction,and 244 component-related target genes and 978 pathogenic genes for gout were obtained.The KEGG pathway analysis revealed the co-pathways for gout decoction and gout,including pathway in cancer,NOD-like receptor signaling pathway,Toll-like receptor signaling pathway,and T cell receptor signaling pathway,among which pathway in cancer was the most critical one.The most critical target in the pathways was TP53,which was targeted by compounds including quercetin in Smilax glabra and Carthamus tinctorius,luteolin in Carthamus tinctorius,and wogonin in Rhizoma Atractylodis.The target prediction found that the number of actual targets interacting with TP53 was 59 for quercetin,25 for luteolin,and 2 for wogonin.FLT3 and MAOA were selected from

关 键 词：痛风汤 痛风 中药药理学 网络药理学 分子对接 

分 类 号：R285.5[医药卫生—中药学]